Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin

M S Hwang1, Y N Yum, J H Joo

  • 1National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul. hyunsung@kfda.go.kr

Anticancer Research
|November 29, 2001
PubMed

Insights

Hypericin, a tyrosine kinase inhibitor, effectively reduces ovarian cancer cell growth by inhibiting the c-erbB-2 oncoprotein and inducing apoptosis. This study shows hypericin

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The c-erbB-2 oncogene, a component of the epidermal growth factor receptor (EGFR), is overexpressed in 20-30% of breast and ovarian adenocarcinomas, correlating with poor patient prognosis.
  • Hypericin, a known protein tyrosine kinase inhibitor, exhibits anti-tumor and anti-viral properties.

Purpose of the Study:

  • To investigate the effects of hypericin on c-erbB-2 oncoprotein activity and downstream kinases.
  • To evaluate hypericin's impact on ovarian cancer cell metastasis.
  • To determine if hypericin-induced cell death in SK-OV-3 cells is linked to c-erbB-2 inhibition.

Main Methods:

  • MTT assay to determine IC50.
  • Morphological and flow cytometric assays to assess apoptosis.
  • Monoclonal anti-erbB-2 antibody for protein expression analysis.
  • Western blotting for downstream kinase activity (MEK, ERK1/2).
  • Invasion and gelatin zymography assays for metastasis-related factors.

Main Results:

  • Hypericin demonstrated an IC50 of 7.5 microM in SK-OV-3 cells after 72 hours.
  • Apoptosis was induced by 5 microM hypericin within 24 hours.
  • Hypericin inhibited c-erbB-2 protein expression and autophosphorylation, as well as MEK and ERK1/2 activity.
  • Upregulation of p21WAF1 and downregulation of Bcl-2 were observed.
  • Hypericin inhibited SK-OV-3 cell invasion but did not affect matrix metalloproteinase (MMP) secretion.

Conclusions:

  • Hypericin effectively inhibits the growth of SK-OV-3 ovarian cancer cells.
  • Hypericin acts by inhibiting c-erbB-2 autophosphorylation and downstream signaling pathways.
  • Hypericin induces apoptosis and may possess anti-invasive properties in ovarian cancer.

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